Abstract: Unintentional medication discrepancies during transitions in care (such as hospitalization and subsequent discharge) are very common and represent a major threat to patient safety. One solution to this problem is medication reconciliation. In response to Joint Commission requirements, most hospitals have developed medication reconciliation processes, but some have been more successful than others, and there are reports of pro-forma compliance without substantial improvements in patient safety. There is now collective experience about effective approaches to medication reconciliation, but these have yet to be consolidated, evaluated rigorously, and disseminated effectively. The broad, long-term objective of this research is to optimize, widely implement, and evaluate medication reconciliation interventions that improve patient safety during transitions in care. The specific aims are to: 1) develop a toolkit consolidating current best practice recommendations for medication reconciliation; 2) conduct a multi-center mentored quality improvement project in which each site adapts the tools for its own environment and implements them to make measurable progress in several facets of the medication reconciliation process; 3) assess the effects of this intervention on unintentional medication discrepancies; and 4) conduct rigorous program evaluation to determine the most important components of the intervention and how best to implement it. Based on expert recommendations from a recent conference on medication reconciliation sponsored by the Society of Hospital Medicine and funded by AHRQ, investigators will engage a steering committee and conduct a second conference to operationalize these recommendations into a set of best practice guidelines, standards, and tools to be adapted by each of 6 participating sites. After training mentors and developing data collection tools, a mentored quality improvement project will be conducted for 21 months, in which each site works to improve medication reconciliation using the toolkit and with mentorship in the form of two site visits and monthly phone calls. Sites will be given assistance with data collection, including data collection tools, on- site training in their use, and a second visit to ensure reliable data collection. Unintentional medication discrepancies at admission and discharge will be analyzed monthly using interrupted time-series methods to track the effects of the individual facets of the intervention over time, adjusted for temporal trends and site- specific effects. Program evaluation will be conducted using mixed qualitative and quantitative methods in order to understand factors that contribute to successfully achieving medication reconciliation goals. This project's findings will provide valuable lessons to all hospitals regarding the best ways to design and implement medication reconciliation interventions to improve medication safety during transitions in care.